Inside Paul Allen’s Plan to Reverse-Engineer the Human Brain

Rick Dahms

In 2003, Microsoft cofounder Paul Allen spent $100 million to build the Allen Institute for Brain Science in Seattle. With laser-equipped microscopes and custom brain-slicers, the institute has mapped the brains of mice, monkeys, and humans, showing which genes are turned on—and where—to better understand vision, memory, autism, and other neural phenomena.

Last year Allen ponied up another $300 million to aim the institute at a narrower but more ambitious goal: a complete understanding of how the mouse brain interprets visual information. To succeed, they’ll have to go beyond static gene maps and learn how to watch a living brain in action.

The new method will track electrical activity in neurons—not just in one mouse but many. Called high-throughput electrophysiology, it’s the sort of big-science approach that the federal government is pushing with its Brain Research through Advancing Innovative Neurotechnologies initiative (yes, the acronym is indeed Brain), which the Allen Institute has been instrumental in planning. Allen talked with WIRED about his institute’s first decade and what he hopes it will do in the next.

Of all the things you could have invested in, why brain research?

Well, as a programmer you’re working with very simple structures compared to the brain. So I was always fascinated by how the brain works. I had a retreat with a bunch of scientists and basically polled them about what could be done to move the whole field ahead, and very quickly consensus formed around the idea of doing a complete genetic assay of the mouse brain. It’s an example of industrial-scale science where you bring together a team that’s focused on producing a database just like the Human Genome Project did.

How do you think your investment has paid off so far?

Oh, I think it’s had a real impact. If you talked to neuroscientists, they would say that everybody in the field who has a genetic component to their research uses our database. So that’s rewarding and heartening.

Allen wants to visualize the brain at an unprecedented level of detail. | Allen Institute for Brain Science

But big discoveries didn’t exactly flow from the research.

Look, the genetic data is a big piece of the puzzle, but it’s not the whole. The brain has this amazing level of almost fractal complexity to it. When you start looking at any part of it in detail you realize that it’s much more complex than you thought. If you ask me five years from now, then I’ll be able to say either “I’m excited we had this breakthrough” or “We’ve come up with zero breakthroughs—I’m disappointed.”

Tell me about the new direction the institute is taking.

The basic idea is to instrument the brain at a very fine level of detail and measure all the parameters—from the diversity of cell types to the electrophysiology—in the mouse visual system, and from that reverse-engineer how it works. That’s an amazing challenge, and no one’s done it yet. We know a certain amount about neurons. You can do fMRI and watch parts of the brain light up. But what happens in the middle is poorly understood. We’re hoping for breakthroughs in understanding cell communication and information flow in the visual system. That’s what I placed a large bet on.

Has it proven more difficult than you thought to translate research into treatments?

We’re not focused on disease pathologies ourselves; we’re trying to focus on basic science. If we understand the basic science, that will help you bring treatments forward. My mother passed away because of Alzheimer’s, so I have a particular interest in helping these things move forward.

How do you decide what to support?

Anybody doing philanthropy has to find something that appeals to them from their own personal background or from intellectual curiosity. It depends on what resonates with you.

You have a basketball team, a football team, and the guitar Jimi Hendrix played at Woodstock. You’ve invested in spaceships, brain research, and gorilla conservation. If my 13-year-old self were a billionaire, this is stuff that would have resonated with me.

I think there’s a through-line from what inspired you when you were younger. Sometimes those things stay with you. If I sit down and say, OK, what are the most exciting problems to work on intellectually, then given my background, these are the ones that appeal the most to me. I just hope they change the world in a positive way.

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